Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ...ribavirin for treating patients with COVID-19.
This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688.
Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days IQR 5–11) than the control group (12 days 8–15; hazard ratio 4·37 95% CI 1·86–10·24, p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir–ritonavir because of biochemical hepatitis. No patients died during the study.
Early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted.
The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.
Abstract
Background
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, designated as a variant of concern by the World Health Organization, carries numerous spike ...mutations that are known to evade neutralizing antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines. A deeper understanding of the susceptibility of omicron variant to vaccine-induced neutralizing antibodies is urgently needed for risk assessment.
Methods
Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the omicron, delta and beta variants to sera from 25 BNT162b2 and 25 CoronaVac vaccine recipients was determined using a live virus microneutralization assay.
Results
The omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains deposited in the GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the omicron variant HKU691 and HKU344-R346K, respectively, whereas none of the CoronaVac recipients had detectable neutralizing antibody titer against either omicron isolate. For BNT162b2 recipients, the geometric mean neutralization antibody titers (GMTs) of the omicron variant isolates (5.43 and 6.42) were 35.7–39.9-fold lower than that of the ancestral virus (229.4), and the GMTs of both omicron variant isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMTs between HKU691 and HKU344-R346K.
Conclusions
Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the omicron variant may be associated with lower COVID-19 vaccine effectiveness.
Immune sera from BNT162b2 and Coronavac recipients had substantially reduced neutralizing antibody titers against the omicron variant. There was no statistically significant difference between the geometric mean neutralization titers against omicron variant strains with or without spike R346K mutation.
Face mask usage by the healthy population in the community to reduce risk of transmission of respiratory viruses remains controversial. We assessed the effect of community-wide mask usage to control ...coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region (HKSAR).
Patients presenting with respiratory symptoms at outpatient clinics or hospital wards were screened for COVID-19 per protocol. Epidemiological analysis was performed for confirmed cases, especially persons acquiring COVID-19 during mask-off and mask-on settings. The incidence of COVID-19 per million population in HKSAR with community-wide masking was compared to that of non-mask-wearing countries which are comparable with HKSAR in terms of population density, healthcare system, BCG vaccination and social distancing measures but not community-wide masking. Compliance of face mask usage in the HKSAR community was monitored.
Within first 100 days (31 December 2019 to 8 April 2020), 961 COVID-19 patients were diagnosed in HKSAR. The COVID-19 incidence in HKSAR (129.0 per million population) was significantly lower (p<0.001) than that of Spain (2983.2), Italy (2250.8), Germany (1241.5), France (1151.6), U.S. (1102.8), U.K. (831.5), Singapore (259.8), and South Korea (200.5). The compliance of face mask usage by HKSAR general public was 96.6% (range: 95.7% to 97.2%). We observed 11 COVID-19 clusters in recreational ‘mask-off’ settings compared to only 3 in workplace ‘mask-on’ settings (p = 0.036 by Chi square test of goodness-of-fit).
Community-wide mask wearing may contribute to the control of COVID-19 by reducing the amount of emission of infected saliva and respiratory droplets from individuals with subclinical or mild COVID-19.
Abstract Background and purpose To assess the therapeutic gains and setbacks as we evolved from the 2-dimensional radiotherapy (2DRT) to conformal 3-dimensional (3DRT) and to intensity-modulated ...(IMRT) era. Materials and methods 1593 consecutive patients from 1994 to 2010 were retrospectively analyzed. Evolving changes in the different era included advances in staging investigation, radiotherapy technique, dose escalation, and use of chemotherapy. Results The 3DRT era achieved significant improvement in local failure-free rate (L-FFR), disease-specific survival (DSS) and overall survival (OS). Neurological damage and bone/soft tissue necrosis were significantly reduced. However, the improvement in distant failure-free rate (D-FFR) was insignificant, and more hearing impairment occurred due to chemotherapy. Significantly higher D-FFR was achieved in the IMRT era, but L-FFR did not show further improvement. 5-Year DSS increased from 78% in the 2DRT, to 81% in the 3DRT, and 85% in the IMRT era, while the corresponding neurological toxicity rate decreased from 7.4% to 3.5% and 1.8%. Conclusions Significant improvement in survival and reduction of serious toxicity was achieved as we evolved from 2DRT to 3DRT and IMRT era; the therapeutic ratio for all T-categories improved with more conformal techniques. Improvements in tumor control were attributed not only to advances in RT technique, but also to better imaging and increasing use of potent chemotherapy. However, it should also be noted that hearing impairment significantly increased due to chemotherapy, L-FFR reached a plateau in the 3DRT era, and it is worrisome that the result for T4 remained unsatisfactory. Besides exploring for more potent chemotherapy and innovative methods, the guideline on dose constraint should be re-visited to optimize the therapeutic ratio.
To study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC).
The treatment outcomes of NPC patients treated with ...IMRT at Pamela Youde Nethersole Eastern Hospital between 2005 and 2007 were reviewed. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. Statistical analyses were performed on dose coverage and locoregional failures.
A total of 193 NPC patients were analyzed; 93% had Stage III/IV disease. Median follow-up was 30 months. Overall disease failure (at any site) developed in 35 patients. Among these, there were 23 distant metastases, 16 local failures, and 9 regional failures. Four of the locoregional failures were marginal. Dose conformity with IMRT was excellent. Patients with at least 66.5 Gy to their target volumes had significantly less locoregional failure. The 2-year local progression-free, regional progression-free, distant metastasis-free, and overall survival rates were 95%, 96%, 90%, and 92%, respectively.
Intensity-modulated radiotherapy provides excellent locoregional control for NPC. Distant metastasis remains the most difficult challenge, and more effective systemic agents should be explored for patients presenting with advanced locoregional diseases.
Abstract
Monitoring population protective immunity against SARS-CoV-2 variants is critical for risk assessment. We hypothesize that Hong Kong’s explosive Omicron BA.2 outbreak in early 2022 could be ...explained by low herd immunity. Our seroprevalence study using sera collected from January to December 2021 shows a very low prevalence of neutralizing antibodies (NAb) against ancestral virus among older adults. The age group-specific prevalence of NAb generally correlates with the vaccination uptake rate, but older adults have a much lower NAb seropositive rate than vaccination uptake rate. For all age groups, the seroprevalence of NAb against Omicron variant is much lower than that against the ancestral virus. Our study suggests that this BA.2 outbreak and the exceptionally high case-fatality rate in the ≥80 year-old age group (9.2%) could be attributed to the lack of protective immunity in the population, especially among the vulnerable older adults, and that ongoing sero-surveillance is essential.
Objectives/Hypothesis
Massive epistaxis due to ruptured pseudoaneurysm of the internal carotid artery (ICA) is an often fatal complication of radiation treatment for patients with nasopharyngeal ...carcinoma. We review the clinical characteristics and predictors of survival in patients suffering from this serious complication after radiotherapy.
Study Design
Retrospective case series.
Methods
Clinical records and radiological investigations of postirradiated NPC patients with ICA pseudoaneurysm diagnosed with digital subtraction angiography in Queen Mary Hospital from January 2003 to December 2012 were reviewed. Risk factors analyzed for survival included gender, size of initial tumor, history of second course of radiotherapy, history of previous maxillary swing nasopharyngectomy, presence of persistent disease, successful initial hemostasis, successful airway control, and endovascular treatment.
Results
Twenty‐six were included in the analysis. Twenty‐three patients underwent endovascular treatment, and 20 (87%) had successful control of the bleeding. Eighteen (69%) patients survived. Univariate analysis showed that successful temporary control of bleeding and airway control were associated with survival.
Conclusions
Prompt bleeding control and airway management is necessary to improve survival. Endovascular treatment is a good definitive treatment option with a high success rate.
Level of Evidence
4 Laryngoscope 124:2292–2296, 2014
Background and Aims
There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of ...SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high‐intensity focused ultrasound (HIFU).
Approach and Results
Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival.
During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time‐to‐progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P < 0.001). The periprocedural toxicity was similar, without any difference in perioperative complications and patient and recurrence‐free survival rates after transplant. Pathological complete response was more frequent after SBRT compared with TACE and HIFU (48.1% vs. 25% vs. 17.9%, respectively; P = 0.037). In multivariable analysis, tumor size <3 cm, listing alpha‐fetoprotein <200 ng/mL, Child A, and SBRT significantly reduced the risk of dropout.
Conclusions
SBRT was safe, with a significantly higher tumor control rate, reduced the risk of waitlist dropout, and should be used as an alternative to conventional bridging therapies.
Summary Background The health benefits of leisure-time physical activity are well known, but whether less exercise than the recommended 150 min a week can have life expectancy benefits is unclear. We ...assessed the health benefits of a range of volumes of physical activity in a Taiwanese population. Methods In this prospective cohort study, 416 175 individuals (199 265 men and 216 910 women) participated in a standard medical screening programme in Taiwan between 1996 and 2008, with an average follow-up of 8·05 years (SD 4·21). On the basis of the amount of weekly exercise indicated in a self-administered questionnaire, participants were placed into one of five categories of exercise volumes: inactive, or low, medium, high, or very high activity. We calculated hazard ratios (HR) for mortality risks for every group compared with the inactive group, and calculated life expectancy for every group. Findings Compared with individuals in the inactive group, those in the low-volume activity group, who exercised for an average of 92 min per week (95% CI 71–112) or 15 min a day (SD 1·8), had a 14% reduced risk of all-cause mortality (0·86, 0·81–0·91), and had a 3 year longer life expectancy. Every additional 15 min of daily exercise beyond the minimum amount of 15 min a day further reduced all-cause mortality by 4% (95% CI 2·5–7·0) and all-cancer mortality by 1% (0·3–4·5). These benefits were applicable to all age groups and both sexes, and to those with cardiovascular disease risks. Individuals who were inactive had a 17% (HR 1·17, 95% CI 1·10–1·24) increased risk of mortality compared with individuals in the low-volume group. Interpretation 15 min a day or 90 min a week of moderate-intensity exercise might be of benefit, even for individuals at risk of cardiovascular disease. Funding Taiwan Department of Health Clinical Trial and Research Center of Excellence and National Health Research Institutes.
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